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Activating mutations in STIM1 and ORAI1 cause overlapping syndromes of tubular myopathy and congenital miosis

2014; National Academy of Sciences; Volume: 111; Issue: 11 Linguagem: Inglês

10.1073/pnas.1312520111

1091-6490

Vasyl Nesin, Graham B. Wiley, Maria Kousi, E‐Ching Ong, Thomas Lehmann, David Nicholl, Mohnish Suri, Nortina Shahrizaila, Nicholas Katsanis, Patrick M. Gaffney, Klaas J. Wierenga, Leonidas Tsiokas,

Pain Mechanisms and Treatments

Significance Stormorken syndrome is a rare autosomal-dominant genetic condition characterized by congenital miosis, bleeding diathesis, thrombocytopenia, and proximal muscle weakness. Other manifestations include functional or anatomical asplenia, ichthyosis, headaches, and dyslexia. A milder form of Stormorken syndrome is associated with muscle weakness and congenital miosis, but without hematologic abnormalities. Here we identify the gene mutations responsible for these syndromes and show that both conditions are caused by the hyperactivation of the Ca 2+ release-activated Ca 2+ (CRAC) channel. These findings contrast the pathologies associated with loss or diminished function of the CRAC channel, provide new molecular insights of the function of the CRAC channel, and suggest new approaches to combat these conditions by blocking CRAC channel activity.